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PMID: 18398687 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression.

Clinical & experimental metastasis ·Vol. 25 ·No. 6 ·2008-00-00 ·Pages 643-55

Hudson LG, Zeineldin R, Stack MS

Abstract

The mesodermally derived normal ovarian surface epithelium (OSE) displays both epithelial and mesenchymal characteristics and exhibits remarkable phenotypic plasticity during post-ovulatory repair. The majority of epithelial ovarian carcinomas (EOC) are derived from the OSE and represent the most lethal of all gynecological malignancies, as most patients (approximately 70%) present at diagnosis with disseminated intra-abdominal metastasis. The predominant pattern of EOC metastasis involves pelvic dissemination rather than lymphatic or hematologic spread, distinguishing EOC from other solid tumors. Acquisition of the metastatic phenotype involves a complex series of interrelated cellular events leading to dissociation (shedding) and dispersal of malignant cells. A key event in this process is disruption of cell-cell contacts via modulation of intercellular junctional components. In contrast to most carcinomas that downregulate E-cadherin expression during tumor progression, a unique feature of primary well-differentiated ovarian cancers is a gain of epithelial features, characterized by an increase in expression of E-cadherin. Subsequent reacquisition of mesenchymal features is observed in more advanced tumors with concomitant loss of E-cadherin expression and/or function during progression to metastasis. The functional consequences of this remarkable phenotypic plasticity are not fully understood, but may play a role in modulation of cell survival in suspension (ascites), chemoresistance, and intraperitoneal anchoring of metastatic lesions.

MeSH Terms
Animals Cadherins/metabolism Disease Progression Epithelium/pathology Female Humans Mesoderm/pathology Neoplasm Invasiveness/pathology Ovarian Neoplasms/metabolism,pathology Phenotype
Chemicals
Cadherins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hudson Laurie G
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
Zeineldin Reema
Stack M Sharon
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Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
0262-0898
DOI
10.1007/s10585-008-9171-5
Published
2008-00-00
Epub
2008-00-09
Pages
643-55
Language
English
Region
Netherlands
NLM ID
8409970
PMCID
PMC2836537
Subset
IM
Grants
NCI NIH HHS · CA86984 · United States
NCI NIH HHS · R01 CA109545-03 · United States
NCI NIH HHS · R01 CA109545-04 · United States
NCI NIH HHS · R01 CA086984-08 · United States
NCI NIH HHS · R01 CA086984 · United States
NCI NIH HHS · CA109545 · United States
NCI NIH HHS · R01 CA086984-09 · United States
NCI NIH HHS · R01 CA109545 · United States
NCI NIH HHS · R01 CA090492 · United States
NCI NIH HHS · R01CA090492 · United States
External Links
PubMed source DOI: 10.1007/s10585-008-9171-5 PMC Full Text View journal details
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